3 years ago

Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: a case-control study

Touhami Mahjoub, Anis Haddad, Mariam Al-Mutawa, Wael Bahia, Wassim Y Almawi, Faouzi Janhani, Aymen Soua, Ramzi R. Finan
Objective To investigate the association of progesterone receptor (PGR) gene variants with the susceptibility to recurrent pregnancy loss (RPL). Design Retrospective case-control study. Setting Outpatient obstetrics/gynecology clinics. Population Women with RPL (396), defined as ≥3 consecutive miscarriages of unknown etiology, and 361 control women. Methods PGR genotyping was done by allelic exclusion method (real-time PCR). Main outcome measures PGR SNPs and the distribution of their alleles, genotypes and haplotypes. Results Higher minor allele frequency (MAF) of rs590688, rs10895068, and rs1942836 was seen in RPL cases than in control women, which remained significant after controlling for multiple comparisons. Significantly higher frequencies of heterozygous (1/2) rs608995, along with heterozygous (1/2) and homozygous (2/2) rs590688, rs10895068, and rs1942836 genotype carriers were seen between RPL cases versus control women, respectively, which persisted after controlling for age, BMI, and menarche. Increased risk of RPL associated with rs590688 and rs1942836 was dependent on the number of minor alleles, thus suggesting a “dose-dependent” effect associated with both variants. Varied linkage disequilibrium (LD) was noted between rs590688, rs10895068, rs608995, and rs1942836 PGR variants associated with RPL. Increased frequency of CGTC, and reduced frequency of GGAT haplotypes was noted in women with RPL compared to control women, thereby assigning RPL susceptible and protective nature to these haplotypes, respectively. This association persisted after controlling for multiple comparisons, and adjusting for covariates. Conclusions This confirms positive association of specific PGR variants (rs590688, rs10895068, and rs1942836), and PGR haplotypes (ATGCCGTC, ATTCGGTC) with increased risk of RPL, thereby supports role for PGR as RPL candidate locus. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/1471-0528.14949

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.